Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5YJ7FI)

• DOT Name: PTB-containing, cubilin and LRP1-interacting protein (PID1)
• Synonyms: P-CLI1; Phosphotyrosine interaction domain-containing protein 1; Protein NYGGF4
• Gene Name: PID1
• Related Disease:
  Glioblastoma multiforme
  Medulloblastoma
  Adult glioblastoma
  Advanced cancer
  Astrocytoma
  Atypical teratoid/rhabdoid tumour
  Brain neoplasm
  Glioma
  Hyperglycemia
  Malignant glioma
  Neoplasm
  Obesity
  Chronic obstructive pulmonary disease
  Cervical cancer
  Cervical carcinoma
• UniProt ID: PCLI1_HUMAN
• Pfam ID: PF14719
• Sequence:
  MFSLPLSLPLCEDTAFLPSKCCSSHKTIKQARTLIMIFLASGTHFQTMLKSKLNVLTLKK
  EPLPAVIFHEPEAIELCTTTPLMKTRTHSGCKVTYLGKVSTTGMQFLSGCTEKPVIELWK
  KHTLAREDVFPANALLEIRPFQVWLHHLDHKGEATVHMDTFQVARIAYCTADHNVSPNIF
  AWVYREINDDLSYQMDCHAVECESKLEAKKLAHAMMEAFRKTFHSMKSDGRIHSNSSSEE
  VSQELESDDG
• Function: Increases proliferation of preadipocytes without affecting adipocytic differentiation.
• Tissue Specificity: Expressed in subcutaneous fat, heart, skeletal muscle, brain, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood leukocyte.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Medulloblastoma	DISZD2ZL	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Astrocytoma	DISL3V18	Strong	Altered Expression	[2]
Atypical teratoid/rhabdoid tumour	DIS1FA0D	Strong	Biomarker	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[3]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Altered Expression	[4]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[5]
Cervical cancer	DISFSHPF	Limited	Genetic Variation	[6]
Cervical carcinoma	DIST4S00	Limited	Genetic Variation	[6]

44 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[13]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[14]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[16]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Amodiaquine	DME4RA8	Approved	Amodiaquine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Etodolac	DM6WJO9	Approved	Etodolac increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Salbutamol	DMN9CWF	Approved	Salbutamol increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Zafirlukast	DMHNQOG	Approved	Zafirlukast increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Fexofenadine	DM17ONX	Approved	Fexofenadine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Entacapone	DMLBVKQ	Approved	Entacapone decreases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Trazodone	DMK1GBJ	Approved	Trazodone increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Promethazine	DM6I5GR	Approved	Promethazine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Ethambutol	DMR87LC	Approved	Ethambutol increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Fludrocortisone	DMUDIR8	Approved	Fludrocortisone increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Amikacin	DM5PDRB	Approved	Amikacin increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Trihexyphenidyl	DMB19L8	Approved	Trihexyphenidyl increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Procyclidine	DMHFJDT	Approved	Procyclidine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Penbutolol	DM4ES8F	Approved	Penbutolol increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Levofloxacin	DMS60RB	Approved	Levofloxacin decreases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Biperiden	DME78OA	Approved	Biperiden increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Alpidem	DMN7Y9K	Approved	Alpidem decreases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Aminosalicylic acid	DMENSL5	Approved	Aminosalicylic acid increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Pirprofen	DMMOFHT	Approved	Pirprofen increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Protriptyline	DMNHTZI	Approved	Protriptyline increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Hydroxyzine	DMF8Y74	Approved	Hydroxyzine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[17]
Nomifensine	DMCP2TS	Withdrawn from market	Nomifensine increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[21]
IPRONIAZIDE	DM42ENF	Investigative	IPRONIAZIDE increases the expression of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[15]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of PTB-containing, cubilin and LRP1-interacting protein (PID1).	[19]

References

• [1] PID1 increases chemotherapy-induced apoptosis in medulloblastoma and glioblastoma cells in a manner that involves NFB.Sci Rep. 2017 Apr 11;7(1):835. doi: 10.1038/s41598-017-00947-6.
• [2] PID1 (NYGGF4), a new growth-inhibitory gene in embryonal brain tumors and gliomas.Clin Cancer Res. 2014 Feb 15;20(4):827-36. doi: 10.1158/1078-0432.CCR-13-2053. Epub 2013 Dec 3.
• [3] PID1 regulates insulin-dependent glucose uptake by controlling intracellular sorting of GLUT4-storage vesicles.Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1592-1603. doi: 10.1016/j.bbadis.2019.03.010. Epub 2019 Mar 21.
• [4] Pid1 induces insulin resistance in both human and mouse skeletal muscle during obesity.Mol Endocrinol. 2013 Sep;27(9):1518-35. doi: 10.1210/me.2013-1048. Epub 2013 Aug 8.
• [5] Association of lung function genes with chronic obstructive pulmonary disease.Lung. 2014 Aug;192(4):473-80. doi: 10.1007/s00408-014-9579-4. Epub 2014 Apr 16.
• [6] Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in cervical cancer: frequent viral integration in topologically destabilized and transcriptionally active chromosomal regions.J Med Virol. 1996 May;49(1):15-22. doi: 10.1002/(SICI)1096-9071(199605)49:1<15::AID-JMV3>3.0.CO;2-N.
• [7] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [8] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [14] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [15] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [16] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [18] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [19] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [21] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.